Introduction

Trientine hydrochloride is a heavy metal antagonist.

Uses for Syprine

Trientine hydrochloride has the following uses:

Trientine hydrochloride is indicated in the treatment of patients with Wilson's disease who are intolerant of penicillamine. Clinical experience with trientine hydrochloride is limited and alternate dosing regimens have not been well characterized; all end points in determining an individual patient's dose have not been well defined. Trientine hydrochloride and penicillamine cannot be considered interchangeable. Trientine hydrochloride should be used when continued treatment with penicillamine is no longer possible because of intolerable or life-endangering side effects.1

Unlike penicillamine, trientine hydrochloride is not recommended in cystinuria or rheumatoid arthritis. The absence of a sulfhydryl moiety renders it incapable of binding cystine and, therefore, it is of no use in cystinuria. In 15 patients with rheumatoid arthritis, trientine hydrochloride was reported not to be effective in improving any clinical or biochemical parameter after 12 weeks of treatment.1

Trientine hydrochloride is not indicated for treatment of biliary cirrhosis.1

Syprine Dosage and Administration

General

Trientine hydrochloride is available in the following dosage form(s) and strength(s):

Trientine hydrochloride capsules, 250 mg, are light brown opaque capsules coded Syprine on one side and ATON 710 on the other.1

Dosage

It isessentialthat the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

Systemic evaluation of dose and/or interval between dose has not been done. However, on limited clinical experience, the recommended initial dose of trientine hydrochloride is 500–750 mg/day for pediatric patients and 750–1250 mg/day for adults given in divided doses 2, 3, or 4 times daily. This may be increased to a maximum of 2000 mg/day for adults or 1500 mg/day for pediatric patients age 12 or under.1

The daily dose of trientine hydrochloride should be increased only when the clinical response is not adequate or the concentration of free serum copper is persistently above 20 mcg/dL. Optimal long-term maintenance dosage should be determined at 6- to 12-month intervals.1

It is important that trientine hydrochloride be given on an empty stomach, at least 1 hour before meals or 2 hours after meals and at least 1 hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed.1

Cautions for Syprine

Contraindications

Hypersensitivity to this product.1

Warnings/Precautions

Warnings

Patient experience with trientine hydrochloride is limited. Patients receiving trientine hydrochloride should remain under regular medical supervision throughout the period of drug administration. Patients (especially women) should be closely monitored for evidence of iron deficiency anemia.1

General Precautions

There are no reports of hypersensitivity in patients who have been administered trientine hydrochloride for Wilson's disease. However, there have been reports of asthma, bronchitis, and dermatitis occurring after prolonged environmental exposure in workers who use trientine hydrochloride as a hardener of epoxy resins. Patients should be observed closely for signs of possible hypersensitivity.1

Specific Populations

Pregnancy

Trientine hydrochloride was teratogenic in rats at doses similar to the human dose. The frequencies of both resorptions and fetal abnormalities, including hemorrhage and edema, increased while fetal copper levels decreased when trientine hydrochloride was given in the maternal diets of rats. There are no adequate and well-controlled studies in pregnant women. Trientine hydrochloride should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.1

Lactation

It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when trientine hydrochloride is administered to a nursing mother.1

Pediatric Use

Controlled studies of the safety and effectiveness of trientine hydrochloride in pediatric patients have not been conducted. It has been used clinically in pediatric patients as young as 6 years with no reported adverse experiences.1

Geriatric Use

Clinical studies of trientine hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience is insufficient to determine differences in responses between the elderly and younger patients. In general, dose selection should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.1

Common Adverse Effects

Clinical experience with trientine hydrochloride has been limited. The following adverse reactions have been reported in a clinical study in patients with Wilson's disease who were on therapy with trientine hydrochloride: iron deficiency, systemic lupus erythematosus. In addition, the following adverse reactions have been reported in marketed use: dystonia, muscular spasm, myasthenia gravis.1

Trientine hydrochloride is not indicated for treatment of biliary cirrhosis, but in one study of 4 patients treated with trientine hydrochloride for primary biliary cirrhosis, the following adverse reactions were reported: heartburn; epigastric pain and tenderness; thickening, fissuring, and flaking of the skin; hypochromic microcytic anemia; acute gastritis; aphthoid ulcers; abdominal pain; melena; anorexia; malaise; cramps; muscle pain; weakness; rhabdomyolysis. A causal relationship of these reactions to drug therapy could not be rejected or established.1

Drug Interactions

Specific Drugs

It isessentialthat the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

In general, mineral supplements should not be given since they may block the absorption of trientine hydrochloride. However, iron deficiency may develop, especially in children and menstruating or pregnant women, or as a result of the low copper diet recommended for Wilson's disease. If necessary, iron may be given in short courses, but since iron and trientine hydrochloride each inhibit absorption of the other, 2 hours should elapse between administration of trientine hydrochloride and iron.1

It is important that trientine hydrochloride be taken on an empty stomach, at least 1 hour before meals or 2 hours after meals and at least 1 hour apart from any other drug, food, or milk. This permits maximum absorption and reduces the likelihood of inactivation of the drug by metal binding in the gastrointestinal tract.1

Actions

Trientine hydrochloride is a chelating compound for removal of excess copper from the body. Wilson's disease (hepatolenticular degeneration) is an autosomal inherited metabolic defect resulting in an inability to maintain a near-zero balance of copper. Excess copper accumulates possibly because the liver lacks the mechanism to excrete free copper into the bile. Hepatocytes store excess copper but when their capacity is exceeded copper is released into the blood and is taken up into extrahepatic sites. This condition is treated with a low copper diet and the use of chelating agents that bind copper to facilitate its excretion from the body.1 Please see product labeling for additional mechanistic action information.

Advice to Patients

Patients should be directed to take trientine hydrochloride on an empty stomach, at least 1 hour before meals or 2 hours after meals and at least 1 hour apart from any other drug, food, or milk. The capsules should be swallowed whole with water and should not be opened or chewed. Because of the potential for contact dermatitis, any site of exposure to the capsule contents should be washed with water promptly. For the first month of treatment, the patient should have temperature taken nightly, and should be asked to report any symptom such as fever or skin eruption.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.